1. JAMA Facial Plastic Surgery: Evidence-Based Medicine and Level of Evidence Primer
John S. Rhee, MD, MPH
Wayne F. Larrabee, Jr, MD

2. 1 What Is Evidence-Based Medicine?
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

3. What Is Evidence-Based Medicine?
“The conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients.” – Sackett et al1
Integration of 3 critical elements
Best research evidence
Clinical expertise
Patient values
1Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn’t. BMJ. 1996;312(7023):71-72.
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

4. What Is Evidence-Based Medicine?
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

5. What Evidence-Based Medicine Is Not
EBM is not “old hat”
“Everyone is doing it already”
EBM is not impossible to practice
EBM is not “cookbook” medicine
EBM is not cost-cutting medicine
EBM is not restricted to randomized controlled trials (RCTs) and meta-analyses
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

6. Case Example
Dr Nash has been in practice for 10 years. He sees a 60-year-old woman in his office who would be a good candidate for a face-lift. Patient asks about “new medicine X” that may decrease postsurgical bruising. He is unsure if he should recommend the use of this medication.
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

7. The MEDLINE Search
MeSH, Google? – rhytidectomy, “new medicine X,” aging face, ???
Limiting the search
Randomized clinical trial (RCT)? Meta-analyses? Cochrane review?
Level of evidence
Best level is 4?
Best level is 2?
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

8. Level of Evidence Table1
Properly powered and conducted RCT, systematic review or meta-analysis of RCTs 2
Well-designed controlled trial without randomization; prospective comparative cohort trial 3
Case-control studies; retrospective cohort study 4
Case series with or without intervention; cross-sectional study 5
Opinion of respected authorities; case reports
Adapted from Oxford Centre for Evidence Based Medicine.
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

9. Level of evidence plays a role in just 1 circle (current best evidence) in the EBM picture
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

10. How to Critique an Original Study: Going Beyond Level of Evidence
Are the results valid?
Patient dropout rate
Length of follow-up
Patient cohort makeup
What are the results?
How large was the treatment effect?
How precise was the estimate of the effect?
How was the effect measured?
Are the results applicable to my patients?
Study patients similar to my patients?
Outcome measures clinically relevant?
Are my surgical skills and techniques similar to those of the study surgeons?
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

11. Incorporate All 3 Elements of EBM
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

12. Case Example (Reprise)
Dr Nash integrates the 3 elements of evidence-based medicine to decide what to do for this patient
Literature review and best evidence level
Best available evidence is 2, no RCTs
Predominantly level 4 evidence supporting efficacy of this medication
Clinical expertise
Comfortable with own surgical procedure and past outcomes without “new medication X”
Surgical cohort in study was predominantly male with different surgical technique, so results may not be applicable for his patient
Patient values
Patient is aware of surgeon experience with procedure and made aware of current level of evidence and accepts recommendations of surgeon not to use “new medication X”
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

13. 2 Facing Levels of Evidence The JAMA Facial Plastic Surgery Initiative
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

14. Levels of Evidence Designation
Only applicable to clinical, therapeutic (disease treatment) studies
Examples include any treatment or interventions in which outcomes are provided
Nonratable articles include (but are not limited to) narrative reviews, editorials, videos, and studies that are basic science, non–human-based, diagnostic, and cadaver/anatomy and survey/questionnaire based
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

15. Building Blocks of Evidence-Based Practice
OCEBM & USPSTF
Individual Studies
Original Articles
Cochrane &
QUORUM
Systematic Reviews
Meta-analyses
GRADE & USPSTF
Clinical Practice Guidelines
Abbreviations: OCEBM, Oxford Centre for Evidence Based Medicine; USPSTF, US Preventive Services Task Force; QUORUM, Quality of Reporting Meta-analyses; GRADE, Grades of Recommendation Assessment, Development, and Evaluation.
Evidence-Based Medicine and Level of Evidence Primer
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •
September 20, 2018 •
Slide 15 15

16. Level of Evidence Table1
Properly powered and conducted RCT, systematic review or meta-analysis of RCTs 2
Well-designed controlled trial without randomization; prospective comparative cohort trial 3
Case-control studies; retrospective cohort study 4
Case series with or without intervention; cross-sectional study 5
Opinion of respected authorities; case reports
Adapted from Oxford Centre for Evidence Based Medicine.
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

17. Study Designs Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

18. Descriptive Studies Observational, nonanalytic
Describe patterns of “distribution of disease”
Person, place, time
Quick, easy, inexpensive
Help in “formulation of hypotheses”
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

19. Case Report – Level of Evidence: 5
Observational, descriptive
Detailed report of an unusual observed characteristic of a single patient
Advantages
Inexpensive
May lead to formulation of hypothesis
Disadvantages
Based on experience of 1 patient
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

20. Case Series – Level of Evidence: 4
Observational, descriptive
Characteristics observed in group of patients
Advantages
Inexpensive
Useful in formulation of hypothesis
Disadvantages
No control group
Bias related to subject or characteristic selection
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

21. Cross-Sectional Studies – Level of Evidence: 4
Observational, descriptive
Data on individual patients at 1 point in time
Exposure and disease measured simultaneously
Prevalence of disease and exposure can be calculated
Useful for formulation of hypothesis about presence of association between exposure and disease
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

22. Cross-Sectional Studies – Level of Evidence: 4
Advantages
Inexpensive
Best design for studying the status quo of disease or condition
Disadvantages
Provide only a “snapshot in time”
“The chicken or the egg” dilemma
Difficult to choose control or comparison group
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

23. Study Designs Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

24. Analytic Studies: Observational or Experimental
Provide information about determinants of disease by testing hypotheses
Observational analytic studies
“Investigator simply observes”
Experimental analytic studies
“Investigator allocates exposure”
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

25. Case-Control Studies – Level of Evidence: 3
Observational, analytic
Cases matched with controls
Cases = those with disease/outcome of interest
Control = comparative group without disease
Past “exposure” is determined
Proportions with the “exposure” within each group are compared
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

26. Case-Control Studies – Level of Evidence: 3
Advantages
Quick and least expensive of analytic designs
Efficient for rare diseases with long latent periods
Disadvantages
Control group selection difficult
Disease incidence rates and relative risks cannot be calculated
Temporal relationship between exposure and disease is sometimes difficult to establish
Prone to selection and recall bias
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

27. Prospective Cohort Studies – Level of Evidence: 2
Observational, analytic
Participants are free of disease/outcome of interest at onset of study
Participants selected on exposure/risk factor under study
Exposed group (treatment group) vs unexposed group
Participants followed over period of time to assess occurrence of disease or outcome
Formulation of incidence rates and relative risk
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

28. Prospective Cohort Studies – Level of Evidence: 2
Advantages
Establishment of temporal relationship between exposure (treatment) and disease
Assessment of multiple effects of a single exposure (treatment)
Calculation of incidence rates and relative risk
Selection bias can be controlled or minimized
Disadvantages
Very time-consuming and expensive
Inefficient for rare diseases
Dropout rate can affect validity of results
An association but not necessarily causation between exposure (treatment) and disease can be made
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

29. Study Designs Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

30. Therapeutic Experimental Studies
Randomized or nonrandomized
Analytic studies
Commonly called clinical trials
Exposure/intervention is controlled or allocated by investigator
Experimental group vs control group
Participants screened for eligibility
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

31. Nonrandomized Clinical Trials – Level of Evidence: 2
Comparison group is historical
Historical controls
Can lead to bias in analysis
Weaker study design due to bias in patient assignment
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

32. Randomized Clinical Trials – Level of Evidence: 1
“Gold standard” in study designs
Randomized assignment to either experimental or control group
Removes potential selection bias
Potential for bias is prevented by blinding the participant to the intervention
Double-blinded = when both investigator and participant are blinded to the intervention
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

33. Randomized Clinical Trials – Level of Evidence: 1
Advantages
Provide strongest evidence for determining causation
Least number of problems or biases
Best design to assess efficacy of a treatment or procedure
Disadvantages
Very expensive and time-consuming
Inefficient if effect of treatment is small
Criteria for measuring outcome may be controversial
Ethical issues
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

34. Meta-analysis Studies – Level of Evidence: 1
Results from published studies combined to provide overall conclusion
Ideally comprised of RCTs only
Smaller sample–sized studies that do not achieve statistical significance are combined
Studies need to be similar with respect to disease and exposure/intervention
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

35. Meta-analysis Studies – Level of Evidence: 1
Advantages
Provide a reliable estimate of most likely effect of an exposure/intervention
Useful for planning future trial with adequate power
Disadvantages
Carry risk of several biases
Meta-analysis of observational studies especially suspect
Too much bias and too many confounding variables
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

36. Systematic Reviews – Level of Evidence: Variable
A thorough and systematic review of the literature targeted by a specific research question
Methods and results should be reproducible and transparent to all
May assign levels of evidence to existing studies
Identify knowledge gaps and point to needed areas of investigation
Dependent on level of evidence of primary literature
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

37. Meta-analysis ≠ Systematic Review
Evidence-Based Medicine and Level of Evidence Primer
September 20, 2018 •

38. JAMA Facial Plastic Surgery: Evidence-Based Medicine and Level of Evidence Primer
John S. Rhee, MD, MPH
Wayne F. Larrabee, Jr, MD
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